Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Recurrent Glioblastoma
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|ClinicalTrials.gov Identifier: NCT02717962|
Recruitment Status : Recruiting
First Posted : March 24, 2016
Last Update Posted : January 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Glioma Glioblastoma Glioblastoma Multiforme GBM Brain Cancer||Drug: VAL-083, Dianhydrogalactitol||Phase 2|
Access to an investigational treatment associated with this study is available outside the clinical trial. More info ...
Recurrent glioblastoma (GBM) is characterized by a dismal prognosis, with a median overall survival of 6-9 months. While a standard of care is established for the initial treatment of GBM - radiation with concurrent and adjuvant temozolomide chemotherapy - management of recurrent disease remains suboptimal. Treatment options include repeat surgery, re-irradiation, or chemotherapy (including experimental targeted therapies, biologic agents, and immunotherapies). Only a minority of patients has response to these treatments, and the resultant benefits in progression-free and overall survival are on the order of weeks to months.
Prognosis and response to therapy are known to be better in patients with a methylated MGMT promoter gene. Epigenetic silencing of MGMT by promoter methylation is an important factor in predicting outcome for patients with GBM treated with temozolomide. Approximately 66% of GBM tumors are MGMT unmethylated (high expression of MGMT), which through a MGMT repair mechanism, confers resistance to temozolomide, the standard chemotherapy treatment of GBM.
VAL-083, Dianhydrogalactitol (DAG), unlike temozolomide, is demonstrated to be active independent of MGMT resistance mechanisms, in vitro. Thus, it may provide a treatment option for those patients that are considered likely to be poor responders to temozolomide.
This is a non-comparative, single arm, biomarker-driven study with VAL-083. Forty-eight (48) eligible patients will receive VAL-083 at 40 mg/m2 IV on days 1, 2, and 3, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation (disease progression, death, intolerable toxicities, investigator's judgment, or withdrawal of consent). Disease status will be evaluated with clinical and MRI evaluation every other 21-day cycle, while the patient is receiving VAL-083 treatment, and then approximately every 42 ± 7 days while remaining on study. Symptom burden will be evaluated using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) completed by patients at baseline and at the time of each imaging evaluation.
Interval medical histories, targeted physical exams, neurologic evaluations, complete blood counts, and other laboratory and safety assessments will be performed approximately every 21-days. Blood samples will be taken at Cycle 1 Day 1 pre-dose, 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of iv infusion with VAL-083 to determine the PK profile and dose-exposure relationship of VAL-083.
Toxicity will be evaluated and documented using the NCI CTCAE version 4.
This study will take approximately 32 months to enroll.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Recurrent Glioblastoma|
|Actual Study Start Date :||January 20, 2017|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||June 2021|
Experimental: VAL-083, Dianhydrogalactitol
VAL-083 at 40 mg/m2 IV on days 1, 2, and 3 of a 21-day treatment-cycle, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation. VAL-083 will be administered as an IV infusion over 30-60 minutes.
Drug: VAL-083, Dianhydrogalactitol
The dosing regimen for patients will be VAL-083 (40 mg/m2) administered IV for 3 consecutive days at the beginning of every 21-day cycle. Patients will continue to receive VAL 083, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation.
- Overall Survival [ Time Frame: Every 30 days from randomization until patient death ]Length of time from start of treatment (Day 1) until patient death
- Estimate Progression-free Survival [ Time Frame: Every 30 days from randomization until disease progression or patient death, whichever occurs earlier ]Time from start of treatment (Day 1) until to the first occurrence of progression or patient death, whichever occurs first
- Estimate Median Progression-Free Survival [ Time Frame: Every 30 days from randomization until disease progression or patient death, whichever occurs earlier ]The median length of time from start of treatment (Day 1) until to the first occurrence of progression or patient death, whichever occurs first
- Estimate Median Overall Survival [ Time Frame: Every 30 days from randomization until patient death ]The median length of time from start of treatment (Day 1) until patient death
- Estimate Overall Response Rate [ Time Frame: Every 42 days from randomization to achievement of either complete response (CR) or partial response (PR) ]Overall number of tumor complete response (CR) or partial response (PR) determined via MRI assessment
- Estimate Duration of Response [ Time Frame: Every 42 days from the first occurrence of a documented, objective response until the time of relapse or patient death ]Length of time tumor continues to demonstrate either complete response (CR) or partial response (PR) via MRI assessment
- Safety evaluation of VAL-083 in patients [ Time Frame: From randomization up to 28 days following last study treatment ]To confirm safety and tolerability of VAL-083 using NCI CTCAE v.4 to assess adverse events
- Quality of Life [ Time Frame: Every 42 days from randomization until disease progression ]MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT)
- Plasma Pharmacokinetics [ Time Frame: Cycle 1 Day 1 predose, 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of iv infusion of VAL-083 ]PK profile and dose-exposure relationship of VAL-083
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02717962
|Contact: Lorena Lopez, B.S.||firstname.lastname@example.org|
|Contact: John Langlands, Ph.D.||email@example.com|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Kathy Hunter, R.N. 713-745-5769 firstname.lastname@example.org|
|Contact: Stephanie Knight, B.S.N., R.N. 713-563-8746 SRKnight@mdanderson.org|
|Principal Investigator: Barbara O'Brien, M.D.|
|Sub-Investigator: Marta Penas-Prado, M.D.|
|Sub-Investigator: Rivkah Cohen, M.D.|
|Sub-Investigator: Carlos Kamiya-Matsuoka, M.D.|
|Sub-Investigator: John DeGroot, M.D.|
|Sub-Investigator: Monica Loghin, M.D.|
|Sub-Investigator: Shiao-Pei Weathers, M.D.|
|Sub-Investigator: W.K. Alfred Yung, M.D.|
|Sub-Investigator: Greg Fuller, M.D.|
|Sub-Investigator: Kenneth Hess, Ph.D.|
|Principal Investigator:||Barbara O'Brien, M.D.||University of Texas, MDAnderson Cancer Center, Houston, Texas, USA 77030|